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Ashish Kamat: Hello, and welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, professor of urologic oncology at MD Anderson Cancer Center. It's a pleasure to welcome once again someone who's very familiar to the audience of this forum, Professor Stephen Williams, who is chief of the division of urology at UTMB. Stephen, honestly, you have so many titles I'm not going to read them out. They're on the screen for those who want to look at them. But really I want to thank you for taking the time and sharing your data, your publication, and your experience in the use of blue light amongst patients and with Equal Access Setting: A Propensity Scored Matching Analysis. Dr. Williams, take it away.

Stephen Williams: All right. Well, first off, I want to thank you, of course, as well as UroToday for the kind invitation. We'll just jump right into this. We performed a propensity score matched analysis, really comparing blue light versus patients that are on white light cystoscopy and really wanted to look at the outcomes, use of treatments, and then also really try to understand the population that may perhaps benefit from the use of blue light cystoscopy.

In our objective, we did compare blue light cystoscopy and the oncologic outcomes in really the largest equal access setting in the United States, the VA health system. Then we assessed specifically the effect of blue light cystoscopy on bladder cancer recurrence, progression, and overall survival.

This is our consort diagram. We actually compared a little under 1,000 patients. However, when we performed a propensity score matched analysis after excluding factors, patients that either did not have a bladder cancer diagnosis or did not have a pathologic assessment of tumors, and more importantly also we wanted to make sure they were confined between this time period that we had between 1997 and 2021 that had at least one year follow-up data, we had 313 patients in each group that underwent either blue light cystoscopy or white light cystoscopy.

This is the statistical analyses that we ended up performing was a Kaplan-Meier curve assessment. Then also really wanted to look at recurrence, free survival progression, and overall survival. Then we conducted three Cox proportional hazard regressions to really try to provide a robust assessment and determine the association in the population that would actually benefit most from the use of blue light versus white light cystoscopy.

We performed a propensity score matched analysis, really excluding patients and really trying to define comparable cohorts. Importantly too with the VA population, it's a minority-majority of the population where we have roughly 10% African-Americans in either group, which is fairly large, particularly for bladder cancer patients. But then we also assess location of bladder cancer diagnosed, VA center versus outside VA center, and smoking, which believe it or not, is sometimes not controlled in some of these large population-based analyses. Then risk stratification, particularly low versus high risk where high risk is defined, those with CIS, Ta high grade, or T1 disease.

Our cohort characteristics, as one can hypothesize, are roughly 99% male. Very few females were included. Median age is about 71 years old, which holds up with bladder cancer patients being diagnosed. Median follow-up period is approximately 3.4 years, slightly longer in those that underwent white light cystoscopy, about 3.7. There were 245 patients deemed low risk, but what's very important is 381 patients, or 61% of the population, the majority of the population were high risk. They were defined as any CIS, T1 or Ta high grade. Then also important, and we published prior, is that 58% of patients received BCG during the study period. What I meant by published before is over 90% of patients receive adequate induction BCG. Then the remainder of patients receive some form of maintenance BCG in the respected time period.

This is our recurrence-free survival, that you could see here that we're able to notice a significantly lower decreased risk of recurrence, particularly for patients that underwent blue light cystoscopy. Where you have close to a hazard ratio of 0.42. In addition, multivariable analysis shows risk of recurrence was still significantly lower for those that had blue light cystoscopy, roughly a 40% decreased risk of recurrence compared to white light. Of course, increasing age as well as also those with high-risk NMIBC had up to a two-fold increased risk of recurrence in this particular study.

In progression-free survival, patients who underwent blue light cystoscopy had a significantly reduced risk of recurrence, roughly 50% decreased risk of recurrence compared to white light and multivariable analysis. Risk of recurrence was still significantly lower following blue light cystoscopy, roughly a 40% decreased risk of recurrence. High-risk NMIBC had up to four times the increased risk of progression, which really also holds suit with other large population-based studies.

Overall survival, we actually noticed also there's roughly a 10% risk of deaths, which homes in on this being really a more significant cohort within the VA population and then also to a majority. I failed to mention roughly 80% were ever smokers. Then there were 16% deaths in the white light cohort. There was improved overall survival, as I mentioned before, of blue light versus white light cystoscopy. The hazard ratio is 0.47. Then worse survival was noted, as one can allude, those that are older as well as those with high-risk NMIBC.

In addition, also, we noticed increased definitive therapy in patients undergoing blue light cystoscopy where we noticed a higher definitive therapy used in the blue light cohort, which also may lead to improved survival outcomes overall. Then also increased use of intravascular treatments is what we noted as well among those that underwent blue light cystoscopy, but this also supports a precision pathway for urologists treating NMIBC.

In conclusion, in the results of the BRAVO study, which is Bladder Cancer Recurrence Analysis in Veterans and Outcomes, performed within the VA healthcare system, we noticed a significantly decreased risk of recurrence, decreased progression, and improved overall survival in patients who underwent blue light cystoscopy compared to those that underwent white light cystoscopy.

There are several limitations to this study, which include its VA population may not be applicable to other populations. In addition, it's an equal access setting where patients may have received equal access that may impact findings as may not be comparable to the general population. In addition, this is a propensity score-matched analysis where although we're trying our best to compare cohorts, it doesn't carry the same weight as one would with a randomized controlled trial.

I want to thank everyone today for their time in allowing me to share this pivotal study, and most importantly, the patients for allowing us to conduct this research, particularly our veterans. Thank you very much.

Ashish Kamat: Thanks a lot, Stephen. Thanks for sharing that study with us and your findings. Just a couple of questions. You brought up the propensity scoring system. Just for the benefit of those among our audience that might not be familiar with what that means, could you just share the methodology, in brief, with everyone?

Stephen Williams: Certainly. Yes, propensity score matched analyses basically look at covariates that we want to compare between two groups. In this case, it's white light cystoscopy and blue light cystoscopy. Then we perform standardized differences where we look for less than 10% so that we could really compare each group apples to apples. In doing so though, we also exclude a number of patients. Like I mentioned before, we had almost a thousand. Then when we drilled down due to performing our propensity score match analysis, it ended up being 616 patients. Roughly 40% of patients are lost. That may lead to other confounding, but we really try to do our best to compare the cohorts.

There's another type of analysis called inverse probability treatment weighting, which gets even more complex, but more importantly, you're able to retain patients and it is another form of methodology. Most important, Dr. Kamat, as you know as well, this does not carry the same weight as a randomized control trial and the power to do so, but it is our attempt, at least in large population-based studies, to essentially try our best, and it's not to replicate, but to compare similar patient populations.

Ashish Kamat: That's a great point because blue light's been studied in prospective randomized trials. That's what led to its approval. Of course, it's approved and it's available for use. Taking the RCT data and then taking your data, putting it all together, if you could share with our audience a little bit about your current practice when it comes to the use of blue light, when do you use it, and how much of the data do you believe, and I believe you believe all of it, and how much do you not believe? What do you think about the photo study, for example? Just your top-level summary on where blue light should be used today?

Stephen Williams: Certainly. Well, regardless of the study, it goes back to the patient population that you're studying. The one thing that I noticed, although the photo is an excellent trial, randomized controlled trial, a really robust analysis, the population was predominantly intermediate risk. Also, among that population, not all received intravascular treatments, such as BCG, which may impact the findings.

In my practice, and as you alluded to, I'm biased because you trained me that I tend to prescribe this more so in a second-stage TURBT type of procedure to really ensure that I'm adequately resecting all the visible tumors. But in patients with high-risk NMIBC is what I tend to, or I have a suspicion for CIS. All this is also performed after which I've assessed the patient in the office. Which brings another caveat to this, and I didn't get into, is flexible blue light cystoscopy. I also utilize this, particularly in the surveillance of patients with high-risk NMIBC. This really helps identify patients hopefully sooner that I may miss with conventional white light.

Then also, going off of the data that you actually provided to us and the world in regards for the use of blue light cystoscopy, I really try to own those results and appropriately prescribe blue light, not one-size-fits-all, but really tailoring and prescribing it to the patients that may actually deem the most benefit.

Ashish Kamat: I think you raise a very good point because people will sometimes look at the indication and say, "Well, I can't use it in all patients that I'm taking to the OR for TURBT." Even though it's approved in that patient population, like you said, we have to select the right people to use it in because we can't just use it on everybody.

On the other hand, it's a little bit of a shame that Storz has withdrawn support for the use of flexible cystoscopy blue light equipment. Again, it's a little rough on our patients who want to have the surveillance in the office and now have to be taken to the OR, but data such as yours just reinforces the real-world findings with blue light and emphasizes that even today, even in the VA system, for example, that using optical-enhanced technology, and in this case, it's blue light, really is to the benefit of our patients. I want to thank you for taking the time to spend with us today and look forward to seeing you soon.

Stephen Williams: Likewise, and thank you so much for inviting me.